ClinVar Miner

Submissions for variant NM_000038.6(APC):c.268A>T (p.Lys90Ter)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003300879 SCV003996958 pathogenic Hereditary cancer-predisposing syndrome 2023-05-01 criteria provided, single submitter clinical testing The p.K90* pathogenic mutation (also known as c.268A>T), located in coding exon 3 of the APC gene, results from an A to T substitution at nucleotide position 268. This changes the amino acid from a lysine to a stop codon within coding exon 3. This alteration was identified in a cohort of 1260 individuals undergoing panel testing for Lynch syndrome due to having a diagnosis of a Lynch-associated cancer and/or polyps (Yurgelun MB et al. Gastroenterology, 2015 Sep;149:604-13.e20). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with APC-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003336838 SCV004045745 pathogenic Familial adenomatous polyposis 1 2023-04-25 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Labcorp Genetics (formerly Invitae), Labcorp RCV003336838 SCV005834481 pathogenic Familial adenomatous polyposis 1 2024-11-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys90*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 2561157). For these reasons, this variant has been classified as Pathogenic.

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